Aplastic Anaemia

Trials and Studies

Study System
Ongoing Clinical Trials
Previous Clinical Trials
Ongoing Retrospective Studies
Key Results of Studies

Study System

To download the documents, click on the titles below

• Graphical Presentation of the Study System of Ongoing or Planned Trials
  36kb 81kb
• Legend to the Study System

Ongoing Clinical Trials

Campath for refractory disease Click here for more details ()

Active Observational Studies 2005:

• Outcome of SAA treatment, IS and BMT in adult vs pediatric patients
• Influence of previous immunosuppressive treatment on the outcome of MUD HSCT
• SAA post hepatitis, how does it differ from other forms, presentation and outcome
• Stem cell source: BM vs PB
• Repeated IS versus alternative donor transplants
• Late clonal disorders
• Outcome of BMT for PNH
• Autologous reconstitution after HSCT
• Fludarabine based regimes for patients over 30 years

Active Prospective Clinical Studies 2005:

• RCT in newly diagnosed SAA, G-CSF vs none and early retreatment vs none
• The use of reduced intensity HSCT from alternative donors in SAA
• MMF in refractory SAA
• Stem Cell Factor pilot study
• Repository of samples of bone marrow failure syndrome patients

Should you be interested in receiving more information about any of the studies listed above please contact Jakob Passweg or Anna Locasciulli

To download the documents, click on the titles below:

• Alternative donor transplants for aplastic anemia: conditioning with fludarabine, cyclophosphamide and antithymocyte globuline
  (A.Bacigalupo - Genoa)
  
  > The first ammendement for this study is availaible here
  
  
• A Randomized Controlled Study in Newly Diagnosed Severe Aplastic Anemia Patients Receiving Antithymocyte Globulin (ATG) and Cyclosporin A, with or without G-CSF (A Tichelli - Basel)
  

Click on the following links to download:

Short Study Overview
Study Protocol (April 2002)
Randomisation Procedures
Case Record Forms (July 2001)

German centres should contact the Trial Co-ordinator or Hubert Schrezenmeier to request an adapted protocol.

Trial Co-ordinator: Kim Champion
Principal Investigator: Andre Tichelli

• A multi-centre pilot study with anti-tnf-α in patients with: 1.fanconi anemia with bone marrow failure lacking compatible bone marrow donor or 2. acquired aplastic anemia resistant to immunosuppressive therapy and lacking bone marrow donor (Carlo Dufour)
  
  
• Mesenchymal stem cells for refractory aplastic anemia. A pilot study of the Aplastic Anemia Working Party of the EBMT (Loic Fouillard)

Previous Clinical Trials

Three recently closed randomised clinical trials (listed below) have addressed the problem of optimal combination of ATG, ciclosporine A and G-CSF for first line treatment of aplastic anaemia: The EBMT trial for patients with severe aplastic anaemia (SAA) compared antithymocyte globulin (ATG) + steroids + ciclosporine A (CSA) versus this combination + G-CSF; the German trial for patients with SAA compared ATG + steroids + CSA with CSA + G-CSF; the EBMT trial for patients with non-severe aplastic anaemia (nSAA) compared ATG + steroids + CSA versus CSA alone.

It turned out that the combination of ATG + steroids + CSA is superior to CSA alone (in treatment of nSAA) and to CSA + G-CSF (in treatment of SAA) in terms of response rate. The EBMT trial in patients with nSAA showed that a second course of immunosuppres-sion is less frequently required in patients who received the combination of ATG + CSA as compared to CSA alone (Marsh et al., BLOOD: 93: 2191-2195; 1999). Therefore an ATG-based regimen in com-bination with CSA is recommended as first-line treatment in patients who are not eligible for BMT from an HLA-identical sibling.

The German trial demonstrated that G-CSF is not able to substitute for the ATG effect. However, patients may show a good neutrophil response to G-CSF. In the EBMT trial the number of severe infections was lower in the G-CSF group. Final analyses of both studies (in particular, regarding long-term effects) are still pending.

The WP SAA prepared a group of randomised trials for treatment of aplastic anaemia by immunosuppression, growth factors and alternative donor transplantation in patients who are not eligible for sibling BMT. The overall strategy is depicted in the figure. In contrast to previous trials that focused in first line treatment of newly diagnosed patients the current scheme provides assignments for further treat-ments in patients failing to respond to the first line therapy.

For further details, please refer to documents under Study System

Treatment of aplastic anaemia with Antilymphocyte Glubulin (ALG) Cyclosporin (CS) with or without a short course of G-CSF: A GITMO / EBMT study for patients with neutrophil counts >0.5x10^9/L
(A.Bacigalupo - Genoa)

A Randomized Controlled Study of r-MetHusSCF in Newly Diagnosed Severe or Very Severe Aplastic Anemia Patients Receiving Antithymocyte Globulin (ATG), Cyclosporin A, and Filgrastim (H Schrezenmeier - Berlin)

Bone marrow transplantation for aplastic anemia: A randomized controlled study of two conditioning regimens (Cyclophosphamide Alone vs. Cyclophosphamide + ATG)
(JR Passweg - Basel)

The EBMT trial for patients with severe aplastic anaemia (SAA) compared antithymocyte globulin (ATG) + steroids + ciclosporine A (CSA) versus this combination + G-CSF
(A Bacigalupo, E Gluckman)
See: Br J Haematol. 2002 Dec;119(4):1075-82.

The German trial for patients with SAA compared ATG + steroids + CSA with CSA + G-CSF
(A Raghavachar, H Schrezenmeier)

The EBMT trial for patients with non-severe aplastic anaemia (nSAA) compared ATG + steroids + CSA versus CSA alone (Blood, 93: 2191-2195, 1999)
(J Marsh)

Ongoing Retrospective Studies

• Comparison of allogeneic bone marrow and peripheral blood stem cell transplantation for aplastic anaemia
• Comparison of outcome of children and adults after immunosuppression or stem cell transplantation for aplastic anaemia
• Comparison of outcome after repeated immunosuppressive treatment or alternative donor stem cell transplantation in aplastic anaemia patients failing to respond to initial immunosuppression
• Impact of number of immunosuppressive treatment prior to (alternative donor) SCT on outcome
• Malignant disorders after treatment of aplastic anaemia
• Autologous recovery after SCT for aplastic anemia
• Allogeneic stem cell transplantation for paroxysmal nocturnal hemoglobinuria.
  
  

Key Results of Studies

The Key Results to the following studies can be downloaded here:

• Immunosuppressive therapy for aplastic anaemia in children: a more severe disease predicts better survival.
  
  
• Results and follow-up of a phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia.
  
  
• Outcome of pregnancy and disease course among women with aplastic anemia treated with immunosuppression.
  
  
• Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial.
  
  
• Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO).

Click here to download a document summarising the Key Results of the following studies:

• Prospective randomised multi-centre study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with non-severe aplastic anaemia

• Haemopoietic growth factors in aplastic anaemia: a cautionary note

• Effectiveness of immunosuppressive therapy in older patients with aplastic anaemia

• Malignant tumours occurring after treatment of aplastic anaemia